Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570162 | SCV000674644 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-11 | criteria provided, single submitter | clinical testing | The p.M208V variant (also known as c.622A>G), located in coding exon 5 of the RAD50 gene, results from an A to G substitution at nucleotide position 622. The methionine at codon 208 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than120000alleles tested) in our clinical cohort.This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico Since supporting evidence is limited at this time, the clinical significance of this alterationremains unclear.analyses, respectively. |
| Invitae | RCV000570162 | SCV001561575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-18 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 486243). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 208 of the RAD50 protein (p.Met208Val). |